Estrogen pretreatment protects males against hypoxia-induced immune depression

Abstract

. Estrogen pretreatment protects males against hypoxia-induced immune depression. Am J Physiol Cell Physiol 282: C1087-C1092, 2002. First published December 12, 2001 10.1152/ajpcell.00454.2001.-Hypoxemia depresses cell-mediated immune functions in males, whereas proestrous females do not show such a depression. We hypothesized that elevated systemic estradiol levels in proestrous females prevent hypoxemia-induced immune depression. To study this hypothesis, male C3H/HeN mice were pretreated with 17␤-estradiol (E 2, 40 g/kg body wt sc) or vehicle for 3 days before induction of hypoxemia and again immediately before induction of hypoxia. The mice were subjected to hypoxemia (95% N 2-5% O2) or sham hypoxemia (room air) for 60 min, and plasma and spleen cells were collected 2 h later. In vehicle-treated mice, splenocyte proliferation and interleukin-2 and interleukin-3 production were depressed after hypoxemia. E 2-pretreated animals, however, displayed no such depression in splenic T cell parameters after hypoxemia. Splenic macrophage cytokine production was also depressed in vehicle-treated mice subjected to hypoxia, whereas it was normal in E 2-pretreated mice. In summary, these findings indicate that administration of E 2 before hypoxemia prevented the depression of cell-mediated immune functions. Thus administration of 17␤-estradiol in high-risk patients before major surgery might decrease hypoxemia-induced immune depression under those conditions.

Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

“…In accordance, several studies reported a splenic immunodepression 2 h and 4 h following laparotomy and hemorrhagic shock [12, 15, 20–23, 41, 42]. In contrast, splenic immune depression after femoral fracture and hemorrhage seems to appear later in the posttraumatic course.…”

Sex differences and estrogen modulation of the cellular immune response after injury

“…Interestingly, earlier time points also showed differences due to estrogen. At two hours after injury, the release of IL-1β and IL-6 by splenic and peritoneal macrophages from proestrus mice was maintained [65] or increased [37] after injury, whereas the release of IL-1β and IL-6 by macrophages from OVX mice was depressed by approximately 50% compared to proestrus female mice. In contrast, trauma/hemorrhage resulted in a 4-fold increase in production of TNF-α by Kupffer cells from OVX females and a 5-fold increase in plasma concentrations of TNF-α in comparison to cells isolated from intact females.…”

Influence of Sex and Age on Mods and Cytokines After Multiple Injuries

“…Lower levels of proinflammatory cytokines prevent infiltration of immunocompetent cells, an important step in the development of organ dysfunction. As a therapeutic approach, estrogen administration in males prevents immunosuppression in various experimental animal models (14). Other studies have shown salutary effects of estrogen and flutamide on cardiac function, which are mediated via a direct effect on intrinsic cells (15,16).…”